Cas6

Cas6 is a family of RNA endoribonucleases associated with CRISPR-Cas adaptive immune systems. Its primary function is to process precursor CRISPR RNA (pre-crRNA) into mature crRNA by cleaving within the CRISPR repeat. This maturation step generates crRNAs that carry a sequence-derived spacer and a signature 5' handle derived from the repeat, which are then loaded into effector complexes to target invading nucleic acids.

Cas6 enzymes are found mainly in archaea and in some bacteria. They occur in several CRISPR-Cas types, most notably type I and type III, but are absent or divergent in many type II systems, where different maturation pathways prevail. The Cas6 family includes several homologous subtypes (for example Cas6a, Cas6b, Cas6c, Cas6d) that vary in sequence and sometimes in substrate preference, reflecting adaptation to different CRISPR repeats. Many Cas6 proteins function as monomers or as dimers and exhibit a compact two-domain fold characteristic of the RAMP (repeat-associated mysterious proteins) superfamily.

Biochemical studies have shown that Cas6 enzymes recognize the structural features of CRISPR repeats and catalyze site-specific cleavage of pre-crRNA. Catalysis can be metal-dependent or metal-independent depending on the organism and Cas6 variant. The mature crRNA is subsequently incorporated into the corresponding surveillance complexes (such as Cascade in type I or Csm/Cmr in type III).

Evolutionarily, Cas6 co-evolves with CRISPR repeats, and horizontal transfer of cas genes has been observed across species. Cas6 remains a focus for understanding crRNA biogenesis and for exploring potential biotechnological applications in RNA processing.